Objective：To investigate the association of C-Reactive Protein（CRP）gene polymorphisms with low high-density lipoprotein cholesterol. Methods：Subjects were recruited by epidemiological cluster sampling in 2009 from Guanlin and Xushe town of Yixing city，and 4156 individuals were confirmed for final analysis. All subjects had completed physical examination and extracted of peripheral blood tests on an empty stomach blood lipids and other biochemical indicators in the morning. TaqMan probe method for four CRP gene SNPs genotyping. Multiple logistic regression was applied to further evaluate relationships between the SNPs and low-HDL-C. Results：The levels of hsCRP were significantly differet among rs1205 and rs876537 genotypes，P < 0.001. Rs876537 and rs1205 were significantly associated with decreased HDL-C，and the recessive model was statistically significant. The polymorphisms of rs1205 and rs876537 were significantly associated with low-HDL-C in the hs-CRP []1.0 mg/L group. Rs10737175 variation was significantly associated with low HDL-C in the hs-CRP normal group. Female with rs1205，rs10737175，rs876537 TT genotype were more likely to suffer from low-HDL-C. Female with rs10737175 TT genotype had a lower HDL-C level than CC+TT carriers. Conclusions：CRP polymorphisms were negatively associated with low-HDL-C level. The CRP gene rs1205，rs1073715 and rs876537 variations were associated with a significant reduction of HDL-C， and the association deserves more attention in the female population especially.